Zygomycosis is a serious fungal infection of humans involving several ubiquitous phycomycetes and which occurs predominantly in individuals with pre-existing chronic debilitating diseases, including diabetes. The precise mechanisms by which diabetes enhances the pathogenicity of these fungi is unknown. Studies have implied that in diabetes ketoacidosis is the major pre-disposing factor, but individuals who are not in a ketotic state will also become infected. All of the previous studies with diabetic animals were conducted using alloxan-induced diabetes, which does not resemble adult-onset diabetes found in humans. The proposed study will examine (A) the relationship between diabetes and zygomycosis using genetically diabetic mice (the diabetic state observed in these mice more closely resembles the adult-onset diabetes found in humans), (B) the physiological factors associated with diabetes as a function of infection, (C) the relationship between the length of time in the diabetic state and infection, and (D) the relationship between ketoacidosis and pathogenicity using streptozotocin to induce this state.